A two dimensional gel technique (isoelectric focusing in the first dimension and SDS gradient gel electrophoresis in the second dimension) recently developed in this laboratory has been used to characterize the pancreatic secretory proteins of the guinea pig, dog, and rabbit. This technique will now be used for a definitive study of human pancreatic secretory proteins. Pancreatic juice already on hand will be used to characterize the proteins by isoelectric point, molecular weight, mass proportion, and actual or potential enzymatic activity. Pancreatic tissue taken from cadaver kidney transplant donors maintained by ex-vivo respiration will provide a series of normal glands from which the genetic variability among pancreatic proteins can be determined. Direct cannulation of the pancreatic duct under endoscopic control will provide samples of pure pancreatic juice from patients with pancreatic cancer and chronic pancreatitis. Qualitative and quantitative variations in the two-dimensional pattern of pancreatic proteins will be correlated with the disease state. If an additional protein(s) appears in the two-dimensional gel analysis of juice from patients with pancreatic cancer, then the protein(s) will be isolated, antibodies will be raised and a radioimmunoassay will be developed. Additional studies will be performed on juice samples from patients to assess the functional state of secreted zymogens.